Genetic functions of the NAIP family of inflammasome receptors for bacterial ligands in mice

Yue Zhao, Jianjin Shi, Xuyan Shi, Yupeng Wang, Fengchao Wang, and Feng Shao

Speaker: Yeh, Zheng-Wei (葉正偉)                                   Time: 13:00~14:00, Mar 22, 2017

Commentator:Chang, Chih-Peng, PhD (張志鵬老師)              Place: Room 601

Abstract:

NAIP proteins, belonging to the NLR family, act as innate immune  sensors that recognize different bacterial ligands. Sensing their ligands, NAIPs recruit an inflammasome protein NLRC4 and gather 8~10 NLRC4 molecules to form a wheel-shaped complex called NAIP/NLRC4 inflammasome. NAIP/NLRC4 inflammasome is one of canonical inflammasome that activates caspase-1 activation and triggers subsequent cytokines maturation, production or pyroptosis as well. Hyperactivation of NAIP/NLRC4 inflammasome can cause severe systemic inflammation, even leading to lethality for the host. Previous studies about NAIP/NLRC4 inflammasome used to focus on functions of NLRC4 but the roles of NAIPs were mainly studied in cells. Thus, in this paper, authors tried to find out in vivo functional roles of NAIPs in NAIP/NLRC4 inflammasome activation as well as defense against bacterial infection. NAIP knockout mice were generated for investigating their roles in vivo and ex vivo. After ligand stimulations, authors found that NAIPs differentially recognized their distinct PAMPs from bacterial T3SS (type 3 secretion system) in cells or mice. Upon bacterial infections to cells, caspase-1 activation and cell death activated by NAIP/NLRC4 inflammasome were dependent on bacterial species and even time points of infections. For in vivo infections, authors noticed that NAIP could sense ligands from bacteria to activate NLRC4 inflammasome and then to defend bacterial infection in mice.

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